The invention relates to a method for enhancing wound healing.
Immobilization is a basic therapeutic principle in wound healing, common to the treatment of lesions of all kinds. Casts, plates, and sutures minimize the negative effects of muscle tension on healing tissues. Since tension is one of the chief factors determining the degree of scar formation, this principle also holds true in skin lesions. The carefully-planned execution of an elective skin incision frequently achieves the best aesthetic result.
Surgeons have been seeking techniques and methods to reduce excessive scar formation, especially in the face. Many approaches have been undertaken to overcome the negative influence of muscular tension on the wound healing process, including various suture techniques, steroid injections, undermining wound edges, and placing incisions in a line parallel to relaxed skin tension lines (RSTLs).
The etiology of skin tension lines, first described more than a century ago, has been subject to controversy over the years. There is general agreement, however, that skin tension lines influence the healing of incisions according to their relative positions. There is evidence that the formation of RSTLs is a dynamic process over time. Studies on fetal calves and human fetal skin suggest that RSTLs are not genetically determined, but represent a change of texture of the skin secondary to extrinsic and/or intrinsic forces. Lorenz, H. P. et al., Development, 114(1):253-259, (1992). This change in texture gives skin certain mechanical characteristics that are retained even when excised. Muscle tension is thought to be a major factor in the formation of RSTLs.
Increased skin tension has a negative effect on wound healing, causing hypertrophic scars or wound dehiscence. See, for example, Sherris, D. A. et al., Otolaryngologic Clinics of North America, 28(5): 1957-1968, 1995. Repeated microtrauma, caused by continuous displacement of injured tissue, induces a prolonged inflammatory response and an increased metabolic activity during the healing process. As a consequence, extracellular deposition of collagen and glycosaminoglycans can intensify and lead to hypertrophic scars. The incidence of hypertrophic scars is higher in certain anatomic areas where there is increased muscular movement. McCarthy, J. G., Plastic Surgery, 1990, Vol. 1, Philadelphia, W B Saunders, page 44.
The invention is based, in part, on a new therapy for management of both traumatic and iatrogenic wounds, which includes the elimination of the tension acting on the wound. The new therapy includes injection of a chemodenervating agent to paralyze muscles capable of exerting tension on such wounds, providing better wound healing with minimal scar development. In addition, early immobilization in elective procedures also allows a surgeon to use finer sutures, further improving the cosmetic result.
In one aspect, the invention features a method for treating a patient having a wound (e.g., a facial wound). The method includes locally administering an amount of a chemodenervating agent such that healing of the wound is enhanced. The chemodenervating agent can be, for example, a botulinum toxin, saxitoxin, tetanus toxin, or tetrodotoxin, and is typically administered by injection. The botulinum toxin can be botulinum toxin A, B, C, D, E, F, or G, and in particular botulinum toxin A or B. The method further can include administering an amount of a local anesthetic agent and/or a local vasoconstrictive agent effective to enhance wound healing. Local anesthetic agents such as lidocaine, bupivacaine, or mepivacaine, or local vasoconstrictive agents can be administered prior to injection with the chemodenervating agent or simultaneously with the chemodenervating agent.
A composition having a chemodenervating agent, a local anesthetic, and a local vasoconstrictive agent also is featured.
In another aspect, the invention features an article of manufacture that includes packaging material and an amount of a chemodenervating agent. The packaging material includes a label that indicates the chemodenervating agent is useful for treating a patient having a wound. Administration of the chemodenervating agent enhances healing of the wound. The chemodenervating agent can be a botulinum toxin such as botulinum toxin A. The article of manufacture also can include a local anesthetic agent or a vasconstrictive agent.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used to practice the invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.